The goal of this project is to determine the metabolic fate of the thyroid hormones, including their overall disposal rates in vivo and mechanisms for their uptake by tissues, their binding to tissue components including receptors, and their metabolic transformations. In vitro studies will assess the uptake and metabolism of hormones by tissues from laboratory animals sacrificed at varying ages, subjected to various stresses, or treated with drugs which are known to alter thyroid hormone economy. Metabolic inhibitors and tissue fractionation procedures will also be employed to characterize hormone degrading systems. Both radio-chemical and immunoassay techniques will be used to identify hormone metabolites, including those derived by partial deiodination, conjugation, and deamination-decarboxylation. Concomitant studies will be performed of hormone metabolism in man, with special reference to rates of conversion of thyroxine to triiodothyronine in various conditions, including recovery from burns, chronic hemodialysis, and hyperlipidemias. In these human studies, assays will be performed to determine the impact of varying conversion rates on basal metabolism, lipid metabolism, and the metabolism of various fuels.